Activation of lung myofibroblasts (LMF) is responsible for the development of lung fibrosis in chronic lung diseases of all causes and remarkably, LMF clearance by apoptosis may prevent development of lung fibrosis and lung injury, and possibly allow recovery from reversal of lung fibrosis. There is full agreement among tissue fibrosis experts that inhibiting o reversing myofibroblast activation (the therapeutic target) is critical fr the treatment of lung fibrosis. Both preventing progression of lung fibrosis as well as possibly, regression of lung fibrosis in spite of continued lung injury, as we documented in our pre-clinical studies, are considered important clinical targets for patients with Idiopathic Pulmonary Fibrosis (IPF). Finally, blocking the progression of lung fibrosis may decrease development of lung cancer. The basis for our Research and Development is the development of novel 'humanized' peptoids (not previously reported). We created a library using analog synthesis to improve potential pitfalls for human therapy. We have performed in a step-wise manner assays to select the safest and most efficient 'humanized' peptoids (including apoptosis assays in activated primary human myofibroblasts; cell-free caspase 8 activation assays; lung injury/fibrogenesis models; preliminary toxicology assays in mice). We have developed novel and highly effective anti-fibrotic peptoids in animal models, with no evidences of immunogenicity in state-of-the-art T-cell assays and with exceptional stability in mouse microsomal systems and mouse blood. The lead peptoid has excellent solubility in water. These features should facilitate administration by inhalation with increased bioavailability to the LMF during clinical trials. The proposed compounds markedly inhibit activation of human and mouse myofibroblast in culture. These compounds were not toxic in the preliminary toxicology studies, including pilot toxicogenomics, to mice at least at 100-fold the therapeutic dose. The aims that are proposed for this Phase-1 STTR are: Specific Aim 1: Efficacy of the Lead Peptoid in Lung Fibrosis Mouse Models. Specific Aim 2: Pharmacokinetics (Single and Multiple doses) in Mice and Stability Assays in vitro in Human Lung Microsomes and Human Plasma. There is no medication for the treatment of lung fibrosis in IPF. Completion of these tasks for the proposed compounds will allow us proceeding with a Phase-2 STTR and clinical development in patients with IPF.